Protocol for the "Chemobrain in Motion - study" (CIM - study): a randomized placebo-controlled trial of the impact of a high-intensity interval endurance training on cancer related cognitive impairments in women with breast cancer receiving first-line chemotherapy

Abstract

Background: Up to 80% of breast cancer patients suffer from Cancer Related Cognitive Impairments (CRCI). Exercise is suggested as a potential supportive care option to reduce cognitive decline in cancer patients. This study will investigate the effects of a high-intensity interval endurance training (HIIT) on CRCI in breast cancer patients. Potentially underlying immunological and neurobiological mechanisms, as well as effects on patients' self-perceived cognitive functioning and common cancer related side-effects, will be explored.

Methods: A single-blinded randomized controlled trial will be carried out. The impact of HIIT on CRCI will be compared to that of a placebo-intervention (supervised myofascial release training). Both interventions will be conducted simultaneously with the patients' first-line chemotherapy treatment typically lasting 12-18 weeks. Fifty-nine women with breast cancer will be included in each of the two groups. The study is powered to detect (α = .05, β = .2) a medium effect size difference between the two groups (d = .5) in terms of patients' change in cognitive testing performances, from baseline until the end of the exercise-intervention. The cognitive test battery, recommended by the International Cancer and Cognition Task Force to assess CRCI, will be used as primary measure. This includes the Hopkins Verbal Learning Test (learning/verbal memory), the Controlled Oral Word Association Test (verbal fluency) and the Trail-Making-Test A/B (attention/set-switching). The following endpoints will be assessed as secondary measures: Go-/No-Go test performance (response inhibition), self-perceived cognitive functioning, serum levels of pro- and antiinflammatory markers (tumor necrosis factor alpha, Interleukin-6, Interleukin-1 alpha, Interleukin-1 beta, C-reactive protein, Interleukin-1 receptor antagonist and Interleukin-10), serum levels of neurotrophic and growth factors (brain-derived neurotrophic factor, insulin-like growth factor 1 and vascular endothelial growth factor), as well as common cancer-related side effects (decrease in physical capacity, fatigue, anxiety and depression, sleep disturbances, quality of life and chemotherapy compliance).

Discussion: This study will provide data on the question whether HIIT is an effective supportive therapy that alleviates CRCI in breast cancer patients. Moreover, the present study will help shed light on the underlying mechanisms of potential CRCI improving effects of exercise in breast cancer patients.

Trial registration: DRKS.de, German Clinical Trials Register (DRKS), ID: DRKS00011390 , Registered on 17 January 2018.

Keywords: Breast cancer; Cancer; Chemobrain; Cognition; Exercise; High-intensity interval endurance training.

Conflict of interest statement

Ethics approval and consent to participate

Ethical approval has been obtained from the Ethics Commission of the Legal Department of the Hessen Regional Medical Council (Germany) (reference number: FF175/2016). The trial is registered at drks.de (ID: DRKS00011390) prior to starting recruitment. Patients will be informed about the possible risks and benefits of the study. Participation in this study will be voluntary. Written informed consent will be obtained from all patients.

Consent for publication

Not applicable.

Competing interests

The authors declare that they have no competing interests.

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Figures

Fig. 1

Flowchart of the trial. (1) Baseline measurement will be conducted shortly after diagnosis and 1–3 days before beginning of patients’ medical treatment; (2) Participants allocated to the high-intensity interval endurance training perform 3 × 3 min high-intensive intervals, interspersed by 90 s active rest-intervals during the first 8 weeks of their chemotherapy (duration ≈ 20–25 min). During the second half of participants’ chemotherapy, the number of intervals will be increased to 5 (duration ≈ 30–35 min); (2) Participants allocated to the Placebo Control Group receive a supervised myofascial release training program, inducing hardly any muscular effort and cardiovascular stimulation. Duration of sessions in the Placebo Control Group correspond to the duration of sessions in the high-intensity interval endurance training

Fig. 2

The schedule of enrolment, interventions and assessments. -t0 during the process of enrolment, t0 baseline, t1 after completion of exercise intervention (equivalent to the end of the patients’ first-line chemotherapy), t2 6 months after completion of exercise intervention, HIIT high-intensity interval endurance training; Placebo control group training (supervised myofascial release training), HVLT-R Hopkins Verbal Learning Test - Revised, COWAT Controlled Oral Word Association Test, TMT Trail Making Test part A/part B, INHIB Response Inhibition Test, FACT-COG Functional Assessment of Cancer Therapy – Cognitive function, TNF-α tumor necrosis factor alpha, IL-6 Interleukin-6, IL-1α Interleukin-1 Alpha, IL-1β Interleukin-1 Beta, CRP C-reactive protein, IL-1RA Interleukin-1 receptor antagonist, IL-10 Interleukin-10, BDNF brain-derived neurotrophic factor, VEGF vascular endothelial growth factor, IGF-1 insulin-like growth factor 1, IXT incremental exercise test, MFI-20 The multidimensional Fatigue Inventory, EORTC-QLQ-C30 core questionnaire 30 items of the European Organization for Research and Treatment of Cancer, HADS-D German version of the Hospital Anxiety and Depression Scale PSQI Pittsburgh Sleeping Quality Index. * As demographic data: age, sex, education, socioeconomic status will be captured. ** As anthropometric data height, weight and BMI will be captured